· preosteoblasts differentiate into osteoblasts
· osteoblasts lay down bone matrix (osteoid)
· matrix mineralises
· immature woven bone produced
· osteoblasts become osteocytes
· osteoclasts appear and resorb bone
· mature lamellar bone formed
· process can occur
· in cartilage (enchondral)
· in fibrous tissue (intramembranous)
· on existing bone (appositional)
· shape of bone determined by
· genome and gene expression
· movement and mechanical forces
· can be disturbed by extrinsic forces
· mesenchyme forms bone without cartilage anlage
· occurs in
· facial bones
· cranial vault bones
· pelvic bones
· part of clavicle
· part of mandible
· membrane bones form from mesenchymal condensations
· condensations are structural analogues of the presumptive bone
· primary ossification centres form
· small groups of cells differentiate into osteoblasts and aggregate
· osteoblasts lay down spicules and islands of bone matrix
· matrix mineralises
· osteoblasts cover surface of spicules and islands and add new matrix
· intramembranous ossification then continues centrifugally
· clavicle is first foetal bone to undergo membranous ossification
· ossifies by 8th gestational week
· intially forms two ossification centres that coalesce into single primary ossification centre
· develops hyaline cartilage (secondary cartilage) during process
· forms physis (secondary growth centre) at proximal end
· is one of last areas to commence secondary ossification and last to undergo epiphyseodesis
· also involved in membranous ossification
· diaphyseal cortex of developing tubular bone derived from perichondrium (periosteum) surrounding cartilaginous model
· undersurface differentiates into osteoblasts
· these deposit parallel plates of lamellar bone
· mesenchyme forms cartilage anlage which forms bone
· primary developmental process of skeleton
· may recur after maturation as fracture repair (maturation of callus)
· process is continuum that may be arbitrarily divided into phases
Basic anlage
· condensations occurs in mesenchyme
· forms precartilagenous basic anlage
· completed by end of 6th gestational week
Cartilagenous anlage
· cells differentiate into chondrocytes
· secrete extracellular ground substance (matrix)
· forms hyaline cartilage model
· produces miniature outline of bone to be
· completed by end of 7th gestational week
Primary collar
· chondrocytes in centre of anlage hypertrophy
· increased biochemical activity in the hypertrophic cells leads to calcification of matrix
· cells in inner layer of perichondrium encircling middle of cartilagenous anlage increase in number
· cells (osteoblasts) lay down periosteal collar of bone by intramembranous ossification
· forms primary bone collar
· comprises multiple rings
· completed by end of 8th gestational week
Primary ossification centre
· fibrovascular tissue enters from bone collar into hypertrophic cells at midshaft of anlage
· bring in osteoblasts and chondroclasts
· calcified cartilage removed and replaced by bone
· process extends towards ends of anlage
· periosteum and bone collar concomitantly extends towards ends of anlage
· combined process forms primary ossification centre
· forms diaphysis and metaphyses
Physis
· orderly arrangement of cells develops adjacent to expanding primary ossification centre
· forms physis
· definitive physis forms at end of 3rd / start of 4th gestational month
Medullary cavity
· central cancellous bone resorbed
· capillary bud brings in myeloid precursor cells
· cells proliferate to form marrow
· endochondral ossification now limited to physes
· same process
· chondrocytes enlarge and become vacuolated
· matrix calcified
· invading cells from metaphysis penetrate cartilaginous base and lay down bone on calcified cartilage bars
· longitudinal growth occurs by continued addition of cartilage at top of plate and continued replacement of calcified cartilage by bone and bottom of plate
· growth plates move further apart from each other
· secondary centre of ossification develops at different time for different bones
· called epiphysis
· chondroepiphyses develop cartilage canals extending inwards from multiple sites in perichondrium
· these participate in forming secondary ossification centres in chondroepiphysis
· secondary ossification is primarily a postnatal process
· distal femoral ossification centre forms just before birth
Reserve zone
· syn. resting zone, germinal zone
· lies immediately adjacent to epiphysis
· sparse single cells
· separated by large amount of matrix
· cells store materials for later nutritional requirements
· lipids, glycogen and proteoglycan aggregates
· cells do not divide
Proliferative zone
· flattened cells
· aligned in longitudinal columns
· function of cells is
· matrix production
· cellular proliferation
· combination leads to longitudinal growth
· these are only cells in growth plate to divide
· top cell is ‘mother’ cell
· cells accumulate glycogen and calcium
· rich vascular supply with high oxygen concentration
Hypertrophic zone
· cells enlarged and spherical
· as move down zone, cells progressively
· enlarge
· consume glycogen
· release calcium from mitochondria
· become vacuolated
· die
· matrix becomes progressively calcified with formation of hydroxyapatite crystals
· function of cells is to
· prepare matrix for calcification
· calcify matrix
· zone has poor vascularity and low oxygen tension
· divided into three subzones
· zone of maturation
· zone of degeneration
· zone of provisional calcification
· starts just distal to last intact transverse septum at base of cell column of cartilage portion
· ends at narrowing of diaphysis
· there is vascular invasion of hypertrophic zone with laying down of bone by osteoblasts
· forms primary spongiosa
· further down, bone laid down on cartilaginous septae removed
· forms secondary spongiosa
· further down, original woven bone replaced by lamellar bone
· called remodelling
· function of zone is
· vascular invasion of transverse septa
· bone formation
· remodelling
· growth plate encircled by
· wedge-shaped groove of cells called the ossification groove or the groove of Ranvier
· ring of fibrous tissue and bone (periosteal collar) called the ring of LaCroix
· groove of Ranvier contributes chondrocytes to growth plate for diametric growth
· ring of LaCroix provides
· mechanical support for weak bone-cartilage junction of growth plate
· progenitor cells for periosteum
· supplied by epipyseal artery
· branches of artery pass through reserve zone and end in upper part of proliferative zone
· supplied by two types of arteries
1. terminal branches of nutrient artery
· supply 4/5 of metaphysis
2. metaphyseal arteries
· supply peripheral metaphysis
· terminal branches from both pass vertically to growth plate
· end in vascular loops just below last intact transverse septum
· no vessels pass from metaphysis to growth plate
· supplied by perichondrial arteries
· proliferative zone supplied by epiphyseal artery as above
· no vessels in hypertrophic zone, ie. avascular
· increases in diameter by appositional (intramembranous) ossification
· near birth, bones consist primarily of trabeculae orientated longitudinally and cylindrically
· trabeculae contain woven bone
· small marrow cavity
· near full term, lamellar bone begins to develop
· cortical thickness and trabecular orientation form according to intraosseous stress patterns (Wolff's law)
· bone formation increases in areas of compression and decreases in areas of tension
· compression side is electronegative and osteoblasts stimulated
· tension side is electropositive and osteoclasts stimulated
· occurs during
· periosteal enlargement of bones
· bone modelling and remodelling
· oseoblasts align on existing bone surface
· cells synthesise osteoid in layers
· osteoid mineralises